title: Gadd45 stress sensors in preeclampsia.
abstract: Preeclampsia is a pregnancy-induced complex of multiple pathological changes. Numerous stresses during pregnancy, including hypoxia, immune activation, inflammatory cytokines, and oxidative stress were reported as contributing factors to the preeclamptic pathology. Seeking common sensors of various stressors in preeclampsia is of new interest and can potentially benefit in disease prevention and treatment. Recent studies have highlighted the role of the Gadd45a protein as a stress sensor in preeclampsia. In response to various pathophysiological stressors, notably hypoxia, inflammatory cytokines, and AT1-AAs, Gadd45a activates Mkk3-p38 and or JNK signaling. This, in turn, results in immunological and inflammatory changes as well as triggering the production of circulating factors such as sFlt-1, which are believed to account for many of the pathophysiological-related symptoms of preeclampsia. Activation of inflammatory/immune responses in preeclampsia may function in a feedback loop to maintain elevated expression of Gadd45a protein.
authors.affiliation: Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA, USA, drgeifman@aol.com.
authors.forename: Ossie
authors.initials: O
authors.lastname: Geifman-Holtzman
authors.forename: Yali
authors.initials: Y
authors.lastname: Xiong
authors.forename: Eliezer J
authors.initials: EJ
authors.lastname: Holtzman
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics* / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000276:immunology; D009687:Nuclear Proteins / Q000235:genetics* / Q000276:immunology; D018384:Oxidative Stress; D010920:Placenta / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D011225:Pre-Eclampsia / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D011247:Pregnancy; D015398:Signal Transduction; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000276:immunology; D000097642:GADD45 Proteins
chemical_list: D018797:Cell Cycle Proteins; D016207:Cytokines; D048670:MAP Kinase Kinase 4; D009687:Nuclear Proteins; D040281:Vascular Endothelial Growth Factor Receptor-1; D048051:p38 Mitogen-Activated Protein Kinases; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C501162:FLT1 protein, human